The benzo[c]phenanthridine alkaloids fagaronine and nitidine represent a class of compounds isolated from the Rutaceae family that show potent antitumor activity against L1210 and P388 murine leukemias. Coralyne, a berbenium alkaloid structurally related to the benzo[c]phenanthridines, exhibits antitumor activity against both tumor screens. Studies on the mechanism of action of fagaronine an nitidine indicate that both alkaloids inhibit DNA synthesis is probably by interacting with A:T base pairs. Derivatives of these compounds have been described in J. Med. Chem., 17, 347 (1974), ibid. 18, 66 (1975), ibid. 18, 708 (1975) and J. Pharm. Sci. 66, 1781 (1977) and shown to have antitumor activity.
In addition, Proc. Natl. Acad. Sci U.S.A., 71, 5078 (1974) and J. Med. Chem. 23, 1330 (1980) report that the presence of a positive charge on the nitrogen atom helps to stabilize the complexes formed with DNA. It also is known by those skilled in the art that a variety of thiazole and fused thiazole derivatives also display biological activity, as reported in Indian J. of Chem., 19B, 894 (1980) and Indian J. Chem. 11, 1115 (1973).